This application relates to stabilization and preservation of patient specimens, bodily fluids, therapeutics, personal care products, surface sanitizers or biological reagents.
Diagnostic laboratory tests on patient bodily fluids or tissue specimens provide significant information for disease treatment. These tests aid in discovery of occult disease, early diagnosis after the onset of signs and symptoms, differential diagnosis of various possible diseases, determination of the stage of the disease, estimation of the activity of the disease, detection of recurrence of disease, and measurement of the efficacy of therapy. The diagnostic benefits of many laboratory tests, however, require that the chemical and physical properties of a patient""s sample remain substantially unaltered during transport, i.e., the time required to go from sample collection from the patient to processing and/or testing by the laboratory.
Microbial contamination of a patient""s sample can cause significant changes to its physical and biochemical composition during transport. If the bioburden of a sample is low and the sample is processed within a short time (2 to 4 hours) after collection, the microorganisms present usually will not affect the sample""s chemical properties. However, if the sample can sustain the growth of organisms and the time between collection and processing exceeds 4 hours, the growth and/or metabolism of the microorganisms can alter the chemical and/or physical properties of the sample. For example, the organisms may be able to consume certain components present in the sample such as carbon, nitrogen, or minerals, thus, removing or altering components which were present in the sample at the time of collection. Secondly, as a result of microbial growth, metabolism or death, components which were not present at the time of collection may be released into the sample.
One type of patient sample which is greatly affected by microbial contamination during transport is a urine sample submitted for urinalysis. Urinalysis is a series of tests performed on the urine sample including leukocytes, cast cells, red blood cells, glucose, bilirubin, ketone, specific gravity, pH, protein, urobilinogen, nitrite, and blood. Normal healthy women have 102103 microorganisms present in their urine. Microorganisms can also be introduced into the patient""s urine sample either through a patient""s clinical infection or by inadvertent contamination during the collection process or transport to the laboratory. Since urine samples generally contain sufficient metabolites and other factors required to support the growth and replication of most microorganisms commonly found in urine samples, delays in transport beyond 4 hours can lead to significant changes in the chemical and physical properties of the samples. For example, in one study, common urinary tract contaminants or potential urinary pathogens significantly altered the chemical/physical properties of unpreserved urine held for 8-24 hours or longer at room temperature: false positive reactions for hemoglobin, protein, nitrites, and esterase; false negative reactions for nitrites, glucose, protein and ketones; and substantial changes in pH. Many of these alterations in the chemical properties of the unpreserved urine samples occurred within 8 hours (Dorn, G. L., unpublished).
Laboratory standards recommend that urine samples be analyzed within two hours after collection from the patient to circumvent changes in chemical and physical properties. However, with the emergence of Health Maintenance Organizations (HMO""s), Preferred Physician Organizations (PPO""s), and centralized laboratory testing facilities combined with increasing pressure to be more cost effective through batch processing of samples, it has become increasingly difficult to comply with traditional standards of practice. For example, one study showed that a large percentage of samples submitted for culture within a hospital setting were  greater than 4 hours old prior to processing. (Dorn, et al., xe2x80x9cAdherence to laboratory guidelines: a study on urine specimen transport time,xe2x80x9d Diagnostics and Clinical Testing 27:28-31 (1989)). Another study indicated that all samples submitted to centralized commercial laboratories exceeded the recommended time limits for transport. (Dorn, G. L., xe2x80x9cMicrobial stabilization of antibiotic-containing urine samples by using the FLORASTAT urine transport system,xe2x80x9d J Clin Micro 29:2169-2174 (1991)). In the area of urinalysis, a recent College of American Pathologist Q-Probes Study documented that for inpatients and outpatients, respectively, only 64% and 77% of laboratories were able to meet the 2-hour transport goal 90% of the time. (Howanitz, et al., xe2x80x9cTimeliness of urinalysis: a College of American Pathologists Q-probes study of 346 small hospitals,xe2x80x9d Arch Pathol Lab Med 121:667-672 (1997)).
Since current medical practices often prevent expedient transport of urine samples for urinalysis, and since microorganisms are frequently present in urine samples collected for urinalysis, a method of blocking the deleterious effects of microbial contamination on a urine sample during transport is advantageous in preserving the chemical and physical integrity of the sample. For this purpose, various preservatives for urine samples have been developed and commercialized. Among the active ingredients for these preservatives are: boric acid, mercuric oxide, sodium azide, tartaric acid, and thimerosal (ethylmercurithiosalicylic acid). Boric acid has been reported to be compatible as a preservative used in combination with urinalysis and leukocyte/cast cell analysis. (Porter, I. A. and Brodie, J. 1969. xe2x80x9cBoric acid preservation of urine samples,xe2x80x9d Br Med J2:353-355; Guenther, K. L. and Washington II, J. A. 1981. Evaluation of the B-D urine culture kit,xe2x80x9d J Clin Microbiol 14:628-630).
Despite the commercial availability of preservatives for urine samples, there are significant deficiencies associated with them. For example, many of the active ingredients used in commercially available urine preservative systems present health, flammability, and/or reactivity hazards. According to the National Fire Prevention Association""s health, flammability, and reactivity hazard ratings for chemicals, a short exposure to mercuric oxide and thimerosal could cause death or major residual injury. Although mercury-based systems such as mercuric oxide (Starplex Scientific, Inc., Etobicoke, Ontario, Canada) and thimerosal (Sigma Chemical Co., St. Louis, Mo.) effectively stabilize samples, their high National Fire Protection Association (NFPA) health hazard rating makes them unsuitable for use when large numbers of samples or high volumes of material are being processed. While sodium azide (Sigma Chemical Co.) is also an effective stabilizing material, the health rating assigned to sodium azide indicates that short exposure could cause serious temporary or residual health injury, making it unsuitable for use in high volume processing. While boric acid (Becton Dickinson, Franklin Lakes, N.J.) (Sage, Inc., Crystal Lakes, Ill.) (Bibby Sterlin, Ltd., Dynalab Corp., Rochester, N.Y.) and tartaric acid (Mid-America Health, Niagara Falls, N.Y.) have moderate to low NFPA hazard ratings, they are not cidal and, consequently, do not effectively block the deleterious effects of all microorganisms of interest, potentially causing false negative and false positive urinalysis results when the urine sample is held at room temperature beyond 8 hours. Therefore, as illustrated in the case of urine samples submitted for urinalysis, there is a continuing need for an effective transport system which provides stability of the chemical and physical properties of patient specimens and bodily fluids without exposing patients, healthcare professionals, and laboratory personnel to serious health hazards.
Biological reagents, some of which are often used in diagnostic testing procedures, are also susceptible to chemical and physical alteration due to microbial contamination. These reagents contain substances which are critical to their function but also capable of supporting microbial growth and/or metabolism. Although most biological reagents are manufactured under sterile conditions in sealed containers, low level microbial contamination can occur during manufacturing. During storage, the growth of the contaminating microorganisms can cause chemical and physical changes to the reagent. Moreover, many reagents are sold in multiple-entry containers at volumes which allow the user to repetitively extract small aliquots over time. There exists the possibility of microbial contamination of the reagent at each entry event. One commercially available preservative for reagents is Micr-O-protect(trademark) (Roche Diagnostics, GmbH, Mannheim, Germany), an ethanolic solution of bromonitrodioxane and methylisothiazolone, with a health rating indicating that short exposure could cause serious temporary or residual injury and a flammability rating indicating that it could be ignited under most ambient conditions. Another preservative is the StabilZyme Select(copyright) Conjugate Stabilizer (SurModics, Inc., Eden Prairie, Minn.) which is an aqueous protein-containing mixture preserved with methylisothiazolone and bromonitrodioxane. Yet another line of preservative is ProClin (Supelco Inc., Bellefonte, Pa.) which utilizes 5-chloro-2-methyl-4-isothiazolin3-one and 2-methyl-4-isothiazolin-3-one. Isothiazolone and its derivatives are corrosive to the eyes potentially causing permanent irreversible injury, can cause skin burns or irritation, and are considered toxic to fish and wildlife if permitted to enter the water supply. Bromonitrodioxane is a formaldehyde releaser, and since formaldehyde is carcinogenic and highly flammable in liquid and gaseous forms, bromonitrodioxane is an unfavorable candidate as a preservative for samples processed in high volume. Consequently, there is a need for an environmentally friendly system which can preserve a biological reagent while maintaining its chemical and physical properties.
Preservatives are often added to therapeutics to increase shelf-life and to reduce the possibility of microbial contamination. As in the case of biological reagents, many therapeutics are packaged in multiple-entry containers at volumes which allow the extraction of small aliquots over time. For example, vaccines are routinely provided in multiple entry containers, and for several decades, thimerosal, a mercury-based preservative, has been used in vaccines to prevent contamination and other biologics in multidose containers. The Food and Drug Administration (FDA) has undertaken a review of drugs containing mercury-based preservatives, including thimerosal, in an effort to reduce the concentration of mercury in vaccines and to find alternative preservative formulations that do not contain mercury. (xe2x80x9cRecommendations regarding the use of vaccines that contain thimerosal as a preservative,xe2x80x9d MMWR 48:996-998 Nov. 5, 1999)) Therefore, there is a need to provide safe, effective preservatives for therapeutics which reduce the risk of microbial contamination as well as potential health problems associated with exposure to mercury.
Microbial contamination can also lead to the chemical and/or physical degradation of personal care products such as cosmetics, hand cleansers, lotions, and shampoos. Moreover, contaminated products routinely exhibit diminished performance and contribute to the spread of infection to users.
Work surfaces and equipment in hospitals and laboratories are highly susceptible to microbial contamination. Likewise, surfaces and appliances found in kitchens and bathrooms of households, restaurants, groceries, catering establishments and the like are routinely exposed to microbial contamination. There is a continuing need for environmentally safe, effective sanitizing products capable of reducing the microbial bioburden in these areas as well.
In one aspect, the invention is a system for preserving a sample which may contain microorganisms, the system including an effective amount of a composition comprising a biguanide and at least one other antimicrobial agent, and the composition being cidal to the microorganisms when present in the sample and containing no antimicrobial additive having a National Fire Protection Association health hazard rating higher than moderate. In one embodiment, the biguanide utilized in the system is chlorhexidine. In another embodiment, the composition comprises a biguanide and at least one other antimicrobial agent comprising a compound that reduces the selective permeability of the cell membrane of the microorganisms. In another embodiment, the composition comprises chlorhexidine and at least one other antimicrobial agent comprising a compound that reduces the selective permeability of the cell membrane of the microorganisms. In another embodiment, the composition comprises a biguanide and an aromatic alcohol. In another embodiment, the composition comprises chiorhexidine and an aromatic alcohol. In another embodiment, the composition comprises a biguanide and 2-phenyl ethanol. In another embodiment, the composition comprises chlorhexidine and 2-phenyl ethanol. In another embodiment, the composition comprises a biguanide an aromatic alcohol, and a terpenoid. In another embodiment, the composition comprises chlorhexidine, an aromatic alcohol, and a terpenoid. In another embodiment, the composition comprises a biguanide, 2-phenyl ethanol, and a terpenoid. In another embodiment, the composition comprises chlorhexidine, 2-phenyl ethanol, and a terpenoid. In another embodiment, the composition comprises a biguanide, an aromatic alcohol, and isoeugenol. In another embodiment, the composition comprises chlorhexidine, an aromatic alcohol, and isoeugenol. In another embodiment, the composition comprises a biguanide, 2-phenyl ethanol, and isoeugenol. In another embodiment, the composition comprises chlorhexidine, 2-phenyl ethanol, and isoeugenol. In another embodiment, the composition comprises a biguanide and a propionate. In another embodiment, the composition comprises chlorhexidine and a propionate. In another embodiment, the composition comprises a biguanide and sodium propionate. In another embodiment, the composition comprises chlorhexidine and sodium propionate. In another embodiment, the composition comprises a biguanide, a propionate, and a parahydroxybenzoate. In another embodiment, the composition comprises chlorhexidine, a propionate, and a parahydroxybenzoate. In another embodiment, the composition comprises a biguanide, sodium propionate, and parahydroxybenzoate. In another embodiment, the composition comprises chlorhexidine, sodium propionate, and parahydroxybenzoate. In another embodiment, the composition comprises a biguanide, a propionate, and ethyl parahydroxybenzoate. In another embodiment, the composition comprises chlorhexidine, a propionate, and ethyl parahydroxybenzoate. In another embodiment, the composition comprises a biguanide, sodium propionate, and ethyl parahydroxybenzoate. In another embodiment, the composition comprises chlorhexidine, sodium propionate, and ethyl parahydroxybenzoate. In another embodiment, the composition comprises a biguanide and boric acid or a boric acid derivative. In another embodiment, the composition comprises chlorhexidine and boric acid or a boric acid derivative. In another embodiment, the composition comprises a biguanide, a propionate, and boric acid or a boric acid derivative. In another embodiment, the composition comprises chlorhexidine, a propionate, and boric acid or a boric acid derivative. In another embodiment, the composition comprises a biguanide, sodium propionate, and boric acid or a boric acid derivative. In another embodiment, the composition comprises chlorhexidine, sodium propionate, and boric acid or a boric acid derivative. The system is useful for samples selected from patient specimens, bodily fluids, reagents, therapeutics, personal care products and sanitizable surface.
In another aspect, the invention is a device comprising an accessible, sealable enclosure for containing and preserving a sample which may contain microorganisms, the enclosure containing a composition free of toxins including mercury, mercury containing compounds, formaldehyde, formaldehyde-releasing compounds, and azides which are unsuitable for use in high volume processing, and comprising a biguanide and at least one other antimicrobial agent, the composition being cidal to microorganisms when present in the sample. In one embodiment, the biguanide utilized in the system is chlorhexidine. In another embodiment, the composition comprises a biguanide and at least one other antimicrobial agent comprising a compound that reduces the selective permeability of the cell membrane of the microorganisms. In another embodiment, the composition comprises chlorhexidine and at least one other antimicrobial agent comprising a compound that reduces the selective permeability of the cell membrane of the microorganisms. In another embodiment, the composition comprises a biguanide and an aromatic alcohol. In another embodiment, the composition comprises chlorhexidine and an aromatic alcohol. In another embodiment, the composition comprises a biguanide and 2-phenyl ethanol. In another embodiment, the composition comprises chlorhexidine and 2-phenyl ethanol. In another embodiment, the composition comprises a biguanide an aromatic alcohol, and a terpenoid. In another embodiment, the composition comprises chlorhexidine, an aromatic alcohol, and a terpenoid. In another embodiment, the composition comprises a biguanide, 2-phenyl ethanol, and a terpenoid. In another embodiment, the composition comprises chiorhexidine, 2-phenyl ethanol, and a terpenoid. In another embodiment, the composition comprises a biguanide, an aromatic alcohol, and isoeugenol. In another embodiment, the composition comprises chlorhexidine, an aromatic alcohol, and isoeugenol. In another embodiment, the composition comprises a biguanide, 2-phenyl ethanol, and isoeugenol. In another embodiment, the composition comprises chiorhexidine, 2-phenyl ethanol, and isoeugenol. In another embodiment, the composition comprises a biguanide and a propionate. In another embodiment, the composition comprises chiorhexidine and a propionate. In another embodiment, the composition comprises a biguanide and sodium propionate. In another embodiment, the composition comprises chlorhexidine and sodium propionate. In another embodiment, the composition comprises a biguanide, a propionate, and a parahydroxybenzoate. In another embodiment, the composition comprises chlorhexidine, a propionate, and a parahydroxybenzoate. In another embodiment, the composition comprises a biguanide, sodium propionate, and parahydroxybenzoate. In another embodiment, the composition comprises chlorhexidine, sodium propionate, and parahydroxybenzoate. In another embodiment, the composition comprises a biguanide, a propionate, and ethyl parahydroxybenzoate. In another embodiment, the composition comprises chlorhexidine, a propionate, and ethyl parahydroxybenzoate. In another embodiment, the composition comprises a biguanide, sodium propionate, and ethyl parahydroxybenzoate. In another embodiment, the composition comprises chlorhexidine, sodium propionate, and ethyl parahydroxybenzoate. In another embodiment, the composition comprises a biguanide and boric acid or a boric acid derivative. In another embodiment, the composition comprises chlorhexidine and boric acid or a boric acid derivative. In another embodiment, the composition comprises a biguanide, a propionate, and boric acid or a boric acid derivative. In another embodiment, the composition comprises chlorhexidine, a propionate, and boric acid or a boric acid derivative. In another embodiment, the composition comprises a biguanide, sodium propionate, and boric acid or a boric acid derivative. In another embodiment, the composition comprises chlorhexidine, sodium propionate, and boric acid or a boric acid derivative. The device is useful for samples selected from patient specimens, bodily fluids, reagents, therapeutics, and personal care products.
In another aspect, the invention is an improved method for preserving a sample which may contain microorganisms, the improvement comprising preserving the chemical and physical properties of the sample by mixing the sample with an effective amount of a composition comprising a biguanide and at least one other antimicrobial agent, wherein the composition is cidal to microorganisms when present in the sample. In one embodiment, the biguanide utilized in the system is chlorhexidine. In another embodiment, the composition comprises a biguanide and at least one other antimicrobial agent comprising a compound that reduces the selective permeability of the cell membrane of the microorganisms. In another embodiment, the composition comprises chlorhexidine and at least one other antimicrobial agent comprising a compound that reduces the selective permeability of the cell membrane of the microorganisms. In another embodiment, the composition comprises a biguanide and an aromatic alcohol. In another embodiment, the composition comprises chlorhexidine and an aromatic alcohol. In another embodiment, the composition comprises a biguanide and 2 phenyl ethanol. In another embodiment, the composition comprises chlorhexidine and 2 phenyl ethanol. In another embodiment, the composition comprises a biguanide an aromatic alcohol, and a terpenoid. In another embodiment, the composition comprises chlorhexidine, an aromatic alcohol, and a terpenoid. In another embodiment, the composition comprises a biguanide, 2-phenyl ethanol, and a terpenoid. In another embodiment, the composition comprises chlorhexidine, 2-phenyl ethanol, and a terpenoid. In another embodiment, the composition comprises a biguanide, an aromatic alcohol, and isoeugenol. In another embodiment, the composition comprises chlorhexidine, an aromatic alcohol, and isoeugenol. In another embodiment, the composition comprises a biguanide, 2-phenyl ethanol, and isoeugenol. In another embodiment, the composition comprises chlorhexidine, 2-phenyl ethanol, and isoeugenol. In another embodiment, the composition comprises a biguanide and a propionate. In another embodiment, the composition comprises chlorhexidine and a propionate. In another embodiment, the composition comprises a biguanide and sodium propionate. In another embodiment, the composition comprises chlorhexidine and sodium propionate. In another embodiment, the composition comprises a biguanide, a propionate, and a parahydroxybenzoate. In another embodiment, the composition comprises chlorhexidine, a propionate, and a parahydroxybenzoate. In another embodiment, the composition comprises a biguanide, sodium propionate, and parahydroxybenzoate. In another embodiment, the composition comprises chlorhexidine, sodium propionate, and parahydroxybenzoate. In another embodiment, the composition comprises a biguanide, a propionate, and ethyl parahydroxybenzoate. In another embodiment, the composition comprises chlorhexidine, a propionate, and ethyl parahydroxybenzoate. In another embodiment, the composition comprises a biguanide, sodium propionate, and ethyl parahydroxybenzoate. In another embodiment, the composition comprises chlorhexidine, sodium propionate, and ethyl parahydroxybenzoate. In another embodiment, the composition comprises a biguanide and boric acid or a boric acid derivative. In another embodiment, the composition comprises chlorhexidine and boric acid or a boric acid derivative. In another embodiment, the composition comprises a biguanide, a propionate, and boric acid or a boric acid derivative. In another embodiment, the composition comprises chlorhexidine, a propionate, and boric acid or a boric acid derivative. In another embodiment, the composition comprises a biguanide, sodium propionate, and boric acid or a boric acid derivative. In another embodiment, the composition comprises chlorhexidine, sodium propionate, and boric acid or a boric acid derivative. The device is useful for samples selected from patient specimens, bodily fluids, reagents, therapeutics, and personal care products.
A transport/preservative system has been found which provides safe, effective transport for patient specimens and bodily fluids, and functions as a preservative for biological reagents, therapeutics, and personal care products. The transport/preservative formulations can also be used as safe, effective sanitizers on surfaces, equipment, and appliances.
In describing the features of the transport/preservative system of the present invention, the following terms are defined as given below. The term xe2x80x9ccidalxe2x80x9d is defined as having antimicrobial activity against gram positive and gram negative bacteria and yeasts, wherein the effective antimicrobial strength is sufficient to cause a reduction of at least 2-3 logs in organism count within 24 hours or to cause sufficient damage to the microorganisms present so that their metabolism is arrested to a level at which the microorganisms cannot alter the chemical or physical properties of the sample. Unless otherwise stated, the term xe2x80x9csamplexe2x80x9d refers to either a diagnostic or laboratory sample, bodily fluid, biological reagent, personal care product, or therapeutic. The term xe2x80x9ctherapeuticxe2x80x9d includes topically, subcutaneously, intramuscularly, orally, mucosally, and unguinally administered pharmaceuticals, nutraceuticals, and over-the-counter preparations.
The transport/preservative system of the present invention utilizes antimicrobial agents having low environmental impact to synergistically provide microbiocidal activity. The transport/preservative system of the present invention provides cidal, not static, antimicrobial activity against the majority of microorganisms commonly found in diagnostic samples, biological reagents, personal care products, or therapeutics, thereby effectively reducing the microbial count to levels which will not cause chemical or physical degradation for extended periods of time at room temperature. Use of the transport/preservative system of the present invention does not alter the chemical properties of interest of the sample. For example, the amount of glucose, ketone, protein, urobilinogen, nitrite, and blood in a patient urine sample can be maintained for extended periods of time. Likewise, the transport/preservative system of the present invention does not alter the physical properties of interest of the sample, e.g., presence of leukocytes, cast cells or red blood cells, specific gravity, color, pH, or buffering capacity of a sample. If desired, the morphological integrity of killed microorganisms in samples can be preserved for over 72 hours, thus allowing meaningful microscopic analysis. The major components of the transport/preservative formulations of the present invention which provide its antimicrobial action are shelf-stable and have a moderate to low NFPA hazard rating indicative of environmental safety. The transport/preservative system of the present invention utilizes combinations of at least two antimicrobial components to achieve cidal action against microorganisms while maintaining the chemical and physical integrity of the sample, thus reducing the possibility of the development of resistance in the microorganisms of interest to one particular antimicrobial component. Additionally, the antimicrobial components of the transport/preservative system act synergistically to permit the use of lower effective concentrations of each component, thereby reducing any possible deleterious effects of individual components on the chemical and physical properties of the sample as well as limiting the exposure of patients, healthcare professionals, laboratory personnel, and consumers to the components. The antimicrobial action of the transport/preservative formulations is also sufficient to sanitize surfaces, containers, equipment, appliances and the like. The variety of transport/preservative formulations presented herein include formulations which are compatible with glass, plastic, rubber, and metal, thus permitting use of the transport/preservative system with a wide range of surfaces, containers, device formats, and instrumentation.
The transport/preservative system of the present invention comprises at least two antimicrobial components. By using more than one antimicrobial component, the transport/preservative system increases the probability of controlling the growth and/or metabolism of potentially resistant microorganisms. The effective combination of antimicrobial components must be cidal. For patient samples which require microscopic examination, e.g., urine specimens, the antimicrobial components of the transport/preservative system of the present invention can be selected to preserve gross cellular morphology.
The antimicrobial components of the present invention must be soluble and chemically stable at room temperature in aqueous solutions at effective concentrations. Another characteristic of the antimicrobial components is that, at effective concentrations, they cannot possess sufficient acidity, basicity, or buffering capacity so as to alter the pH of the sample. The antimicrobial components must be stable and effective through a broad pH range, i.e, from about pH 4 to about pH 8. For samples where specific gravity is considered an important parameter, e.g., urine samples, the specific gravity of the antimicrobial components in aqueous solution must be sufficiently similar to water so as to not change the specific gravity of the sample.
Antimicrobial biguanides are one important class of compounds used in the present invention. Among the useful biguanides are chlorhexidine and its derivatives (e.g., chlorhexidine gluconate), the alexidine group, and polymeric biguanides (e.g., polyhexamethylene biguanides). The preferred biguanides are chlorhexidine and its derivatives. It is understood that similar biguanides with bromide and/or iodide ions substituted for the chloride ions can be used in the present invention.
Antimicrobial agents which damage the cell membrane of microorganisms and subsequently reduces or destroys the cell membrane""s selective permeability are also important components of the present invention. These include but are not limited to antimicrobial aromatic alcohols, terpenoids, parahydroxybenzoate esters, deoxycholates, taurocholates, and detergents/surfactants. Suitable antimicrobial aromatic alcohols include but are not limited to phenylethyl alcohol, benzyl alcohol, and phenoxyethyl alcohol. Preferred terpenoids include but are not limited to isoeugenol, isohexanol, and isooctanol. Suitable parahydroxybenzoate esters include but are not limited to alkyl esters such as methyl-, ethyl-, propyl-, and butyl-parahydroxybenzoates as well as the aromatic benzylparahydroxybenzoate. Preferred detergents/surfactants are lipid-active such as octoxynol (Triton-X).
Antimicrobial organic acids are another important class of antimicrobial components of the present invention. Preferred organic acids include but are not limited to acetic, propionic, benzoic, citrate, and sorbic acid and their monvalent salts. In urine transport, ammonium salts are not useful due to their interference in routine diagnostics tests. Most preferred is sodium propionate.
Boric acid and its derivatives are other important antimicrobial components of the present invention. Unlike commercially available specimen transport systems using boric acid to provide microbial stasis, the transport/preservative system of the present invention uses boric acid in combination with other antimicrobial components to provide microbial cidal action.
Optionally, the transport/preservative system of the present invention can comprise fragrance components. Preferably, the fragrance components are antimicrobial. Preferred fragrance components include but are not limited to isoeugenol, ethyl vanillin, and pinacol.
A preferred stabilizing, transport/preservative formulation of the present invention comprises an antimicrobial aromatic alcohol, an alkyl guaiacol, and a biguanide. One example of this formulation, hereinafter referred to as xe2x80x9cChemistat I,xe2x80x9d comprises 2-phenyl ethanol, isoeugenol, and chlorhexidine. Most preferably, Chemistat I formulations comprise 2-phenyl ethanol from about 0 xcexcl/ml to about 2.5 xcexcl/ml, isoeugenol from about 0.2 xcexcl/ml to about 1.5 xcexcl/ml, and chlorhexidine from about 0.01 mg/ml to about 0.1 mg/ml, and any combination thereof. These concentrations and subsequent concentrations for the transport/preservative system reported herein are the final concentration after the sample is added. To preserve urine specimens, the Chemistat I formulation preferably comprises 2-phenyl ethanol at about 1.8 xcexcl/ml, isoeugenol at about 0.2 xcexcl/ml, and chlorhexidine at about 0.02 mg/ml. The Chemistat I formulations are in liquid form, and 2-phenyl ethanol, isoeugenol, and chlorhexidine are all active ingredients. Additionally, 2-phenyl ethanol and isoeugenol provide a synthetic rose scent and a spicy fragrance, respectively, to mask sample odor.